Phenotypes associated with this allele

• Allele Symbol: Tg(MMTVtTA)1Mam
• Allele Name: transgene insertion 1, Lothar Hennighausen
• Allele ID: MGI:3053958
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Dnmt1^tm1(tetO-BCL2)Sjk/Dnmt1^+ Tg(IghMyc)22Bri/0 Tg(MMTVtTA)1Mam/0	involves: 129S4/SvJae * C57BL/6	MGI:3511863
cx2	Tg(MMTVtTA)1Mam/0 Tg(tetO-Eda*A1)1Dsch/0	involves: C57BL/6	MGI:3713128
cx3	Tg(tetO-BCR/ABL1)27Dgt/0 Tg(MMTVtTA)1Mam/0	involves: C57BL/6 * FVB/N * SJL	MGI:3693360
cx4	Tg(tetO-BCR/ABL1)2Dgt/0 Tg(MMTVtTA)1Mam/0	involves: C57BL/6 * FVB/N * SJL	MGI:3693361
cx5	Tg(MMTVtTA)1Mam/0 Tg(tetO-Esr1)#Paf/0	involves: C57BL/6 * FVB/N * SJL	MGI:5296757
cx6	Eda^Ta-6J/Y Tg(MMTVtTA)1Mam/0 Tg(tetO-Eda*A1)1Dsch/0	involves: C57BL/6J	MGI:3713124

Genotype
MGI:3511863

cx1

• Allelic Composition: Dnmt1^{tm1(tetO-BCL2)Sjk}/Dnmt1⁺; Tg(IghMyc)22Bri/0; Tg(MMTVtTA)1Mam/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:93549 )

• without doxycycline treatment median survival is 82 days, with doxycycline treatment the improves to 145 days

neoplasm

increased leukemia incidence ( J:93549 )

• in the absence of doxycycline, lymphoblastic leukemia is seen by 2 weeks of age

• in 5 - 7 week old triple transgenics with lymphoblastic leukemia doxycycline treatment resulted in normalization of the WBC count and restoration of normal hematopoiesis

increased B cell derived lymphoma incidence ( J:93549 )

• bulky B cell derived lymphomas, similar to those in Tg(IghMyc)22Bri single transgenics, are seen in older triple transgenics after treatment with doxycycline

behavior/neurological

lethargy ( J:93549 )

• transgenics with leukemia are lethargic, doxycycline treatment returns activity levels to normal

hematopoietic system

enlarged spleen ( J:93549 )

• in the absence of doxycycline, mutants develop an enlarged spleen with doxycycline treatment the spleen returns to its normal size

immune system

enlarged spleen ( J:93549 )

• in the absence of doxycycline, mutants develop an enlarged spleen with doxycycline treatment the spleen returns to its normal size

growth/size/body

enlarged spleen ( J:93549 )

• in the absence of doxycycline, mutants develop an enlarged spleen with doxycycline treatment the spleen returns to its normal size

Genotype
MGI:3713128

cx2

• Allelic Composition: Tg(MMTVtTA)1Mam/0; Tg(tetO-Eda*A1)1Dsch/0
• Genetic Background: involves: C57BL/6

endocrine/exocrine glands

enlarged Meibomian gland ( J:86628 )

• enlarged meibomian gland in the absence of doxicycline (transgene is expressed)

• however, the preputial gland and sweat glands are normal

sebaceous gland hypertrophy ( J:99510 )

• hypertrophy of sebaceous glands associated with hair follicles of the eyelids

vision/eye

abnormal eyelid morphology ( J:99510 )

• eyelids show a ring of yellow hair with slightly thicker skin around the eyelashes than seen in wild-type

enlarged Meibomian gland ( J:86628 )

• enlarged meibomian gland in the absence of doxicycline (transgene is expressed)

• however, the preputial gland and sweat glands are normal

limbs/digits/tail

limbs/digits/tail phenotype ( J:86628 )

N • in the absence of doxicycline (the transgene is expressed), overall tail morphology is indistinguishable from controls

integument

integument phenotype ( J:86628 )

N • in the absence of doxicycline (the transgene is expressed), overall skin morphology is indistinguishable from controls

enlarged Meibomian gland ( J:86628 )

• enlarged meibomian gland in the absence of doxicycline (transgene is expressed)

• however, the preputial gland and sweat glands are normal

sebaceous gland hypertrophy ( J:99510 )

• hypertrophy of sebaceous glands associated with hair follicles of the eyelids

abnormal guard hair morphology ( J:86628 )

• in the absence of doxicycline (the transgene is expressed), guard hair numbers are somewhat increased to 8.7% compared to 5-6% in wild-type

decreased zigzag hair amount ( J:86628 )

• in the absence of doxicycline), zigzag hair is reduced to about 6% which is at least 6-fold less than in wild-type

• zigzag hair is not restored when the transgene is turned off in adults by the addition of doxicycline, indicating an irreversible role in embryonic stages

Genotype
MGI:3693360

cx3

• Allelic Composition: Tg(tetO-BCR/ABL1)27Dgt/0; Tg(MMTVtTA)1Mam/0
• Genetic Background: involves: C57BL/6 * FVB/N * SJL

mortality/aging

premature death ( J:72377 )

• upon withdrawal of tetracycline (TET), expression of BCR/ABL results in development of lethal leukemia; 100% of bitransgenic mice die by ~76 days

hematopoietic system

enlarged spleen ( J:72377 )

• spleen becomes massively enlarged when TET treatment is stopped

anemia ( J:72377 )

• severe anemia develops in peripheral blood without TET treatment

thrombocytopenia ( J:72377 )

• severe thrombocytopenia in peripheral blood develops when TET treatment is stopped

increased leukocyte cell number ( J:72377 )

• increased peripheral blood leukocyte count is observed 10-20 days after TET withdrawal; blood shows presence of cells resembling immature lymphocytes

• when TET is given to mice in advanced stages of disease, WBC counts normalize in 48-72 hours, lymphoblasts are not detected in peripheral blood

immune system

enlarged spleen ( J:72377 )

• spleen becomes massively enlarged when TET treatment is stopped

increased leukocyte cell number ( J:72377 )

• increased peripheral blood leukocyte count is observed 10-20 days after TET withdrawal; blood shows presence of cells resembling immature lymphocytes

• when TET is given to mice in advanced stages of disease, WBC counts normalize in 48-72 hours, lymphoblasts are not detected in peripheral blood

enlarged lymph nodes ( J:72377 )

• nodes become massively enlarged when TET is stopped; when TET is given to mice in advanced stages of disease, complete regression of enlarged lymph nodes occurs within 5 days

cellular

increased apoptosis ( J:72377 )

• resumption of TET treatment results in ~80% of leukemic cells undergoing apoptosis

skeleton

abnormal bone marrow morphology ( J:72377 )

• bone marrow is pale; hematopoietic cells are replaced by lymphoblasts

neoplasm

increased leukemia incidence ( J:72377 )

• 100% of mice develop acute lymphoblastic leukemia (ALL) upon withdrawal of tetracycline administration

• leukocyte counts range from 80000-150000/ul

• leukemic cells infiltrate skin, pleura, and meninges

growth/size/body

enlarged spleen ( J:72377 )

• spleen becomes massively enlarged when TET treatment is stopped

Genotype
MGI:3693361

cx4

• Allelic Composition: Tg(tetO-BCR/ABL1)2Dgt/0; Tg(MMTVtTA)1Mam/0
• Genetic Background: involves: C57BL/6 * FVB/N * SJL

mortality/aging

premature death ( J:72377 )

• upon withdrawal of tetracycline (TET), expression of BCR/ABL results in development of lethal leukemia; 100% of bitransgenic mice die by ~27 days

hematopoietic system

enlarged spleen ( J:72377 )

• spleen becomes massively enlarged when TET treatment is stopped

anemia ( J:72377 )

• severe anemia develops in peripheral blood without TET treatment

thrombocytopenia ( J:72377 )

• severe thrombocytopenia in peripheral blood develops when TET treatment is stopped

increased leukocyte cell number ( J:72377 )

• increased peripheral blood leukocyte count is observed 6-10 days after TET withdrawal; blood shows presence of cells resembling immature lymphocytes

• when TET is given to mice in advanced stages of disease, WBC counts normalize in 48-72 hours, lymphoblasts are not detected in peripheral blood

immune system

enlarged spleen ( J:72377 )

• spleen becomes massively enlarged when TET treatment is stopped

increased leukocyte cell number ( J:72377 )

• increased peripheral blood leukocyte count is observed 6-10 days after TET withdrawal; blood shows presence of cells resembling immature lymphocytes

• when TET is given to mice in advanced stages of disease, WBC counts normalize in 48-72 hours, lymphoblasts are not detected in peripheral blood

enlarged lymph nodes ( J:72377 )

• nodes become massively enlarged when TET is stopped; when TET is given to mice in advanced stages of disease, complete regression of enlarged lymph nodes occurs within 5 days

cellular

increased apoptosis ( J:72377 )

• spleen becomes massively enlarged

skeleton

abnormal bone marrow morphology ( J:72377 )

• bone marrow is pale; hematopoietic cells are replaced by lymphoblasts

neoplasm

increased leukemia incidence ( J:72377 )

• 100% of mice develop acute lymphoblastic leukemia (ALL) upon withdrawal of tetracycline administration

• leukocyte counts range from 80000-150000/ul

• leukemic cells infiltrate skin, pleura, and meninges

growth/size/body

enlarged spleen ( J:72377 )

• spleen becomes massively enlarged when TET treatment is stopped

Genotype
MGI:5296757

cx5

• Allelic Composition: Tg(MMTVtTA)1Mam/0; Tg(tetO-Esr1)#Paf/0
• Genetic Background: involves: C57BL/6 * FVB/N * SJL

endocrine/exocrine glands

abnormal seminal vesicle morphology ( J:78639 )

♂ • when 14 week old males are removed from doxycycline administration for 50 days, seminal vesicles show a decrease in mass compared to controls

reproductive system

abnormal seminal vesicle morphology ( J:78639 )

♂ • when 14 week old males are removed from doxycycline administration for 50 days, seminal vesicles show a decrease in mass compared to controls

decreased epididymis weight ( J:78639 )

♂ • when 14 week old males are removed from doxycycline administration for 50 days, epididymis weight is decreased compared to controls

abnormal vas deferens morphology ( J:78639 )

♂ • when 14 week old males are removed from doxycycline administration for 50 days, vas deferens weight is decreased compared to controls

short estrus ( J:78639 )

♀ • females raised on doxycycline to block expression of Esr1 exhibit a decrease in the number of days in estrus when the doxycycline is removed and Esr1 is expressed, however overall cycle length is no different from controls

decreased litter size ( J:78639 )

• mutants without doxycycline (expressing Esr1) exhibit a 15% reduction in litter size compared to mutants receiving doxycycline

Genotype
MGI:3713124

cx6

• Allelic Composition: Eda^Ta-6J/Y; Tg(MMTVtTA)1Mam/0; Tg(tetO-Eda*A1)1Dsch/0
• Genetic Background: involves: C57BL/6J

growth/size/body

decreased body weight ( J:86628 )

♂ • at 5 months of age, weight is about 80% of wild-type in the absence of doxicycline

endocrine/exocrine glands

abnormal gland morphology ( J:86628 )

♂ • in the presence of doxicycline throughout embryonic development to suppress Eda-A1 transgene expression, males are identical to Eda^Ta-6J males, showing lack of sweat glands; mice continue to show this phenotype even after withdrawal of doxicycline from the food at 6 months of age

abnormal male preputial gland morphology ( J:86628 )

♂ • preputial gland is not restored by transgene expression

increased sebocyte number ( J:86628 )

♂ • in the absence of doxicycline, sebaceous glands are enlarged relative to wild-type or Eda^Ta-6J males; size of individual sebocytes is the same but the numbers are increased, with excessive production of sebum

absent Meibomian glands ( J:86628 , J:99510 )

♂ • meibomian glands are not restored by transgene expression (J:86628)

♂ • however, Eda transgene expression does restore the sweat glands that are absent in Eda^Ta-6J males (J:86628)

♂ (J:99510)

sebaceous gland hyperplasia ( J:86628 )

♂ • in the absence of doxicycline, sebaceous glands are 200-300% larger than in wild-type or Eda^Ta-6J males; size of individual sebocytes is the same but the numbers are increased

♂ • hyperplasia is seen in both glands associated with each de novo guard follicle and also in the single sebaceous gland associated with each medium follicle

♂ • addition of doxicycline at 3 months of age reverses the hyperplasia of sebaceous glands within 3 months

sebaceous gland hypertrophy ( J:99510 )

♂ • transgene expression results in hypertrophy of sebaceous glands associated with hair follicles of the eyelids

increased sebum secretion ( J:86628 )

♂ • in the absence of doxicycline

vision/eye

absent Meibomian glands ( J:86628 , J:99510 )

♂ • meibomian glands are not restored by transgene expression (J:86628)

♂ • however, Eda transgene expression does restore the sweat glands that are absent in Eda^Ta-6J males (J:86628)

♂ (J:99510)

immune system

immune system phenotype ( J:99510 )

♂N • transgene expression rescues the susceptibility to corneal inflammation seen in Eda^Ta-6J males

reproductive system

abnormal male preputial gland morphology ( J:86628 )

♂ • preputial gland is not restored by transgene expression

renal/urinary system

abnormal male preputial gland morphology ( J:86628 )

♂ • preputial gland is not restored by transgene expression

integument

abnormal male preputial gland morphology ( J:86628 )

♂ • preputial gland is not restored by transgene expression

increased sebocyte number ( J:86628 )

♂ • in the absence of doxicycline, sebaceous glands are enlarged relative to wild-type or Eda^Ta-6J males; size of individual sebocytes is the same but the numbers are increased, with excessive production of sebum

sebaceous gland hyperplasia ( J:86628 )

♂ • in the absence of doxicycline, sebaceous glands are 200-300% larger than in wild-type or Eda^Ta-6J males; size of individual sebocytes is the same but the numbers are increased

♂ • hyperplasia is seen in both glands associated with each de novo guard follicle and also in the single sebaceous gland associated with each medium follicle

♂ • addition of doxicycline at 3 months of age reverses the hyperplasia of sebaceous glands within 3 months

sebaceous gland hypertrophy ( J:99510 )

♂ • transgene expression results in hypertrophy of sebaceous glands associated with hair follicles of the eyelids

increased sebum secretion ( J:86628 )

♂ • in the absence of doxicycline

abnormal coat/ hair morphology ( J:86628 )

♂ • in the absence of doxicycline, the number of medium hairs is increased to a similar extent as in Eda^Ta-6J males

♂ • however, total hair numbers are unchanged

♂ • in the presence of doxicycline throughout embryonic development to suppress Eda-A1 transgene expression, males are identical to Eda^Ta-6J males, showing lack of tail hair, guard hair and zigzag hair; mice continue to show this phenotype even after withdrawal of doxicycline from the food at 6 months of age

abnormal hair growth ( J:86628 )

♂ • in the absence of doxicycline, tail hairs are reduced in number

♂ • however, the hair behind the ears that is missing in Eda^Ta-6J males is fully restored when the transgene is expressed (absence of doxicycline)

short hair ( J:86628 )

♂ • in the absence of doxicycline, tail hairs are reduced in length

disheveled coat ( J:86628 )

♂ • in the absence of doxicycline, mutants have somewhat scruffy disordered coat hair compared to wild-type and Eda^Ta-6J males

absent zigzag hairs ( J:86628 )

♂ • zigzag hairs are not restored by transgene expression (absence of doxicycline)

♂ • however, the number of guard hairs is restored to wild-type levels

abnormal skin morphology ( J:86628 )

♂ • tail ridges on skin surfaces are absent in the absence of doxicycline

absent Meibomian glands ( J:86628 , J:99510 )

♂ • meibomian glands are not restored by transgene expression (J:86628)

♂ • however, Eda transgene expression does restore the sweat glands that are absent in Eda^Ta-6J males (J:86628)

♂ (J:99510)